The aim of the current study was to evaluate the therapeutics potential of eluxadoline (ELX) loaded solid lipid nanoparticles (SLNs) in ulcerative colitis. ELX loaded SLNs were prepared using three different lipids according to the solvent emulsification technique. The optimization of prepared SLNs (F1-F3) were carried out based on size, PDI, zeta potential, percent drug entrapment (%EE), and loading (%DL). The lipid (stearic acid) based SLNs (F2) was optimized with particle size (266.0 ± 6.4 nm), PDI (0.217 ± 0.04), zeta potential (31.2 ± 5.19 mV), EE (65.0 ± 4.8%), and DL (4.60 ± 0.8%). The optimized SLNs (F2) was further evaluated by DSC, FTIR, SEM, in vitro release, and stability studies, which confirmed the successful encapsulation of ELX in SLNs. The efficacy of optimized SLNs (F2) in comparison to the pure ELX drug was assessed in acetic acid induced colitis rat models. It was observed that the delivery of ELX by SLNs alleviated the induced acetic acid colitis significantly. Thus, ELX loaded SLNs delivery to the colon has a significant potential to be developed for the treatment of ulcerative colitis.

Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3–842.2 nm), PDI (0.448–0.853), ζP (−8.21 to −19.7 mV), %EE (48.45–79.36%) and %DL (7.69–19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.

Ribociclib is a newly approved orally administered drug for breast cancer. This study aimed to prepare, characterize, and evaluate hybrid lipid–polymer nanoparticles (PLNs) of ribociclib to enhance its in vitro dissolution rate, pharmacokinetics, and anticancer efficacy. Ribociclib-loaded PLNs were prepared by solvent evaporation using the Box–Behnken design to optimize formulation variables. Particle size, entrapment efficiency, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), in vitro release cytotoxicity, molecular modeling, and pharmacokinetic studies were examined. The ribociclib-loaded PLN (formula 1, F1) was optimized in terms of particle size (266.9 ± 4.61 nm) and encapsulation efficiency (59.1 ± 2.57 mg/mL). DSC and thermogravimetric characterization showed the absence of a crystalline structure in the prepared PLNs, confirmed by FTIR, and showed no interactions between the components and the drug. AFM showed well-dispersed heterogeneously shaped nanoparticles. The in vitro release profile exhibited significant results for the optimized formula, reaching 100% at 600 and 90 min at pH 6.8 and 1.2, respectively. The low IC₅₀ obtained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay suggests that optimized PLN might serve as an effective delivery vehicle for cancer treatment, especially breast and lung cancer. Molecular modeling revealed several hydrogen bonds. A pharmacokinetic study in rats showed that the ribociclib formula had a 6.5-fold increase in maximum concentration (C_max) and a 5.6-fold increase in area under the curve (AUC). Regarding the everted intestinal sac absorption, formula 1 increased ribociclib penetration relative to the physical combination and pure medication. In conclusion, optimized PLNs with enhanced physicochemical and cytotoxic properties and improved pharmacokinetic parameters were successfully prepared.

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 3² full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in C_max and AUC₀–∞ with short t_max compared to the market product (Viagra^®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.

The current study is a randomized, open-label, two-period, two-sequence, two-way crossover pharmacokinetic study in healthy Jordanian subjects to evaluate the pharmacokinetics and bioequivalence profile of two cases of empagliflozin 10 mg under fasting and fed conditions. The plasma concentrations of empagliflozin were determined using an HPLC-MS/MS method. Tolerability and safety were assessed throughout the study. This study included 26 subjects, 26 in both fasting and fed groups.The pharmacokinetic parameters, which included the area under the concentration–time curve from time zero to infinity (AUC_0–inf) and the final quantifiable concentration (AUC_0–last), maximum serum concentration (C_max), and time to reach the maximum drug concentration (T_max) were found to be within an equivalence margin of 80.00–125.00%. The pharmacokinetic profiles show that the empagliflozin test and parent reference cases were bioequivalent in healthy subjects. The two treatments’ safety evaluations were also comparable.